COMPARATIVE ACUTE LETHALITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD), 1,2,3,7,8-PENTACHLORODIBENZO-P-DIOXIN AND 1,2,3,4,7,8-HEXACHLORODIBENZO-P-DIOXIN IN THE MOST TCDD-SUSCEPTIBLE AND THE MOST TCDD-RESISTANT RAT STRAIN

We have previously demonstrated a more than 300-fold difference in acute LD50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) between male Long-Evans (Turku AB; L-E) and Han/Wistar (Kuopio; H/W) rats after intraperitoneal exposure. In the present study, we compared the acute lethality of TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HCDD) in these strains by intragastric administration. In agreement with previous data, H/W rats proved to be strikingly resistant to TCDD, since even the highest dose tested, 7200 mug/kg, was below the LD50 level for both genders. The corresponding LD50 values for female and male L-E rats were 9.8 and 17.7 mug/kg, respectively. A similar strain difference was discovered for PCDD: the LD50 value was > 1620 mug/kg for female H/W rats and between 20 and 60 mug/kg for female L-E rats. Surprisingly, the acute lethality of HCDD did not follow the same pattern. Female H/W rats turned out to be only about 10 times less susceptible to that congener than female L-E rats (LD50 values 1871 and between 120 and 360 mug/kg, respectively). These findings do not support the widely accepted concept that sufficiently high doses of all dioxin congeners will produce the same effects. Either the higher chlorinated dioxins have toxic effects distinct from those of TCDD or the relative contribution of toxic impacts varies among these compounds.